T3DB: Klotho

Name	Klotho
Synonyms	3.2.1.31
Gene Name	KL
Organism	Human
Amino acid sequence	>lcl\|BSEQ0009325\|Klotho MPASAPPRRPRPPPPSLSLLLVLLGLGGRRLRAEPGDGAQTWARFSRPPAPEAAGLFQGT FPDGFLWAVGSAAYQTEGGWQQHGKGASIWDTFTHHPLAPPGDSRNASLPLGAPSPLQPA TGDVASDSYNNVFRDTEALRELGVTHYRFSISWARVLPNGSAGVPNREGLRYYRRLLERL RELGVQPVVTLYHWDLPQRLQDAYGGWANRALADHFRDYAELCFRHFGGQVKYWITIDNP YVVAWHGYATGRLAPGIRGSPRLGYLVAHNLLLAHAKVWHLYNTSFRPTQGGQVSIALSS HWINPRRMTDHSIKECQKSLDFVLGWFAKPVFIDGDYPESMKNNLSSILPDFTESEKKFI KGTADFFALCFGPTLSFQLLDPHMKFRQLESPNLRQLLSWIDLEFNHPQIFIVENGWFVS GTTKRDDAKYMYYLKKFIMETLKAIKLDGVDVIGYTAWSLMDGFEWHRGYSIRRGLFYVD FLSQDKMLLPKSSALFYQKLIEKNGFPPLPENQPLEGTFPCDFAWGVVDNYIQVDTTLSQ FTDLNVYLWDVHHSKRLIKVDGVVTKKRKSYCVDFAAIQPQIALLQEMHVTHFRFSLDWA LILPLGNQSQVNHTILQYYRCMASELVRVNITPVVALWQPMAPNQGLPRLLARQGAWENP YTALAFAEYARLCFQELGHHVKLWITMNEPYTRNMTYSAGHNLLKAHALAWHVYNEKFRH AQNGKISIALQADWIEPACPFSQKDKEVAERVLEFDIGWLAEPIFGSGDYPWVMRDWLNQ RNNFLLPYFTEDEKKLIQGTFDFLALSHYTTILVDSEKEDPIKYNDYLEVQEMTDITWLN SPSQVAVVPWGLRKVLNWLKFKYGDLPMYIISNGIDDGLHAEDDQLRVYYMQNYINEALK AHILDGINLCGYFAYSFNDRTAPRFGLYRYAADQFEPKASMKHYRKIIDSNGFPGPETLE RFCPEEFTVCTECSFFHTRKSLLAFIAFLFFASIISLSLIFYYSKKGRRSYK
Number of residues	1012
Molecular Weight	116179.815
Theoretical pI	Not Available
GO Classification	Functions beta-glucuronidase activity vitamin D binding beta-glucosidase activity signal transducer activity fibroblast growth factor binding Processes positive regulation of bone mineralization axon guidance aging epidermal growth factor receptor signaling pathway innate immune response Fc-epsilon receptor signaling pathway positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway activation of MAPKK activity fibroblast growth factor receptor signaling pathway insulin receptor signaling pathway MAPK cascade neurotrophin TRK receptor signaling pathway Ras protein signal transduction vascular endothelial growth factor receptor signaling pathway calcium ion homeostasis energy reserve metabolic process small GTPase mediated signal transduction phosphatidylinositol-mediated signaling acute inflammatory response carbohydrate metabolic process Components integral component of plasma membrane intracellular extracellular region plasma membrane extracellular space integral component of membrane extracellular exosome
General Function	Vitamin d binding
Specific Function	May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Pfam Domain Function	Glyco_hydro_1 (PF00232 )
Transmembrane Regions	982-1002
GenBank Protein ID	Not Available
UniProtKB ID	Q9UEF7
UniProtKB Entry Name	KLOT_HUMAN
Cellular Location	Cell membrane
Gene sequence	>lcl\|BSEQ0017791\|Klotho (KL) ATGCCCGCCAGCGCCCCGCCGCGCCGCCCGCGGCCGCCGCCGCCGTCGCTGTCGCTGCTG CTGGTGCTGCTGGGCCTGGGCGGCCGCCGCCTGCGTGCGGAGCCGGGCGACGGCGCGCAG ACCTGGGCCCGTTTCTCGCGGCCTCCTGCCCCCGAGGCCGCGGGCCTCTTCCAGGGCACC TTCCCCGACGGCTTCCTCTGGGCCGTGGGCAGCGCCGCCTACCAGACCGAGGGCGGCTGG CAGCAGCACGGCAAGGGTGCGTCCATCTGGGATACGTTCACCCACCACCCCCTGGCACCC CCGGGAGACTCCCGGAACGCCAGTCTGCCGTTGGGCGCCCCGTCGCCGCTGCAGCCCGCC ACCGGGGACGTAGCCAGCGACAGCTACAACAACGTCTTCCGCGACACGGAGGCGCTGCGC GAGCTCGGGGTCACTCACTACCGCTTCTCCATCTCGTGGGCGCGAGTGCTCCCCAATGGC AGCGCGGGCGTCCCCAACCGCGAGGGGCTGCGCTACTACCGGCGCCTGCTGGAGCGGCTG CGGGAGCTGGGCGTGCAGCCCGTGGTCACCCTGTACCACTGGGACCTGCCCCAGCGCCTG CAGGACGCCTACGGCGGCTGGGCCAACCGCGCCCTGGCCGACCACTTCAGGGATTACGCG GAGCTCTGCTTCCGCCACTTCGGCGGTCAGGTCAAGTACTGGATCACCATCGACAACCCC TACGTGGTGGCCTGGCACGGCTACGCCACCGGGCGCCTGGCCCCCGGCATCCGGGGCAGC CCGCGGCTCGGGTACCTGGTGGCGCACAACCTCCTCCTGGCTCATGCCAAAGTCTGGCAT CTCTACAATACTTCTTTCCGTCCCACTCAGGGAGGTCAGGTGTCCATTGCCCTAAGCTCT CACTGGATCAATCCTCGAAGAATGACCGACCACAGCATCAAAGAATGTCAAAAATCTCTG GACTTTGTACTAGGTTGGTTTGCCAAACCCGTATTTATTGATGGTGACTATCCCGAGAGC ATGAAGAATAACCTTTCATCTATTCTGCCTGATTTTACTGAATCTGAGAAAAAGTTCATC AAAGGAACTGCTGACTTTTTTGCTCTTTGCTTTGGACCCACCTTGAGTTTTCAACTTTTG GACCCTCACATGAAGTTCCGCCAATTGGAATCTCCCAACCTGAGGCAACTGCTTTCCTGG ATTGACCTTGAATTTAACCATCCTCAAATATTTATTGTGGAAAATGGCTGGTTTGTCTCA GGGACCACCAAGAGAGATGATGCCAAATATATGTATTACCTCAAAAAGTTCATCATGGAA ACCTTAAAAGCCATCAAGCTGGATGGGGTGGATGTCATCGGGTATACCGCATGGTCCCTC ATGGATGGTTTCGAGTGGCACAGAGGTTACAGCATCAGGCGTGGACTCTTCTATGTTGAC TTTCTAAGCCAGGACAAGATGTTGTTGCCAAAGTCTTCAGCCTTGTTCTACCAAAAGCTG ATAGAGAAAAATGGCTTCCCTCCTTTACCTGAAAATCAGCCCCTAGAAGGGACATTTCCC TGTGACTTTGCTTGGGGAGTTGTTGACAACTACATTCAAGTAGATACCACTCTGTCTCAG TTTACCGACCTGAATGTTTACCTGTGGGATGTCCACCACAGTAAAAGGCTTATTAAAGTG GATGGGGTTGTGACCAAGAAGAGGAAATCCTACTGTGTTGACTTTGCTGCCATCCAGCCC CAGATCGCTTTACTCCAGGAAATGCACGTTACACATTTTCGCTTCTCCCTGGACTGGGCC CTGATTCTCCCTCTGGGTAACCAGTCCCAGGTGAACCACACCATCCTGCAGTACTATCGC TGCATGGCCAGCGAGCTTGTCCGTGTCAACATCACCCCAGTGGTGGCCCTGTGGCAGCCT ATGGCCCCGAACCAAGGACTGCCGCGCCTCCTGGCCAGGCAGGGCGCCTGGGAGAACCCC TACACTGCCCTGGCCTTTGCAGAGTATGCCCGACTGTGCTTTCAAGAGCTCGGCCATCAC GTCAAGCTTTGGATAACGATGAATGAGCCGTATACAAGGAATATGACATACAGTGCTGGC CACAACCTTCTGAAGGCCCATGCCCTGGCTTGGCATGTGTACAATGAAAAGTTTAGGCAT GCTCAGAATGGGAAAATATCCATAGCCTTGCAGGCTGATTGGATAGAACCTGCCTGCCCT TTCTCCCAAAAGGACAAAGAGGTGGCTGAGAGAGTTTTGGAATTTGACATTGGCTGGCTG GCTGAGCCCATTTTCGGCTCTGGAGATTATCCATGGGTGATGAGGGACTGGCTGAACCAA AGAAACAATTTTCTTCTTCCTTATTTCACTGAAGATGAAAAAAAGCTAATCCAGGGTACC TTTGACTTTTTGGCTTTAAGCCATTATACCACCATCCTTGTAGACTCAGAAAAAGAAGAT CCAATAAAATACAATGATTACCTAGAAGTGCAAGAAATGACCGACATCACGTGGCTCAAC TCCCCCAGTCAGGTGGCGGTAGTGCCCTGGGGGTTGCGCAAAGTGCTGAACTGGCTGAAG TTCAAGTACGGAGACCTCCCCATGTACATAATATCCAATGGAATCGATGACGGGCTGCAT GCTGAGGACGACCAGCTGAGGGTGTATTATATGCAGAATTACATAAACGAAGCTCTCAAA GCCCACATACTGGATGGTATCAATCTTTGCGGATACTTTGCTTATTCGTTTAACGACCGC ACAGCTCCGAGGTTTGGCCTCTATCGTTATGCTGCAGATCAGTTTGAGCCCAAGGCATCC ATGAAACATTACAGGAAAATTATTGACAGCAATGGTTTCCCGGGCCCAGAAACTCTGGAA AGATTTTGTCCAGAAGAATTCACCGTGTGTACTGAGTGCAGTTTTTTTCACACCCGAAAG TCTTTACTGGCTTTCATAGCTTTTCTATTTTTTGCTTCTATTATTTCTCTCTCCCTTATA TTTTACTACTCGAAGAAAGGCAGAAGAAGTTACAAATAG
GenBank Gene ID	Not Available
GeneCard ID	Not Available
GenAtlas ID	Not Available
HGNC ID	HGNC:6344
Chromosome Location	13
Locus	Not Available
References	Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI: Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997 Nov 6;390(6655):45-51. 9363890 Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y: Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998 Jan 26;242(3):626-30. 9464267 Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT: The DNA sequence and analysis of human chromosome 13. Nature. 2004 Apr 1;428(6982):522-8. 15057823 Kato Y, Arakawa E, Kinoshita S, Shirai A, Furuya A, Yamano K, Nakamura K, Iida A, Anazawa H, Koh N, Iwano A, Imura A, Fujimori T, Kuro-o M, Hanai N, Takeshige K, Nabeshima Y: Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys. Biochem Biophys Res Commun. 2000 Jan 19;267(2):597-602. 10631108 Yahata K, Mori K, Arai H, Koide S, Ogawa Y, Mukoyama M, Sugawara A, Ozaki S, Tanaka I, Nabeshima Y, Nakao K: Molecular cloning and expression of a novel klotho-related protein. J Mol Med (Berl). 2000;78(7):389-94. 11043382 Koh N, Fujimori T, Nishiguchi S, Tamori A, Shiomi S, Nakatani T, Sugimura K, Kishimoto T, Kinoshita S, Kuroki T, Nabeshima Y: Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun. 2001 Feb 2;280(4):1015-20. 11162628 Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, Fujimori T, Nabeshima Y: Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett. 2004 May 7;565(1-3):143-7. 15135068 Arking DE, Krebsova A, Macek M Sr, Macek M Jr, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC: Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):856-61. Epub 2002 Jan 15. 11792841 Arking DE, Atzmon G, Arking A, Barzilai N, Dietz HC: Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity. Circ Res. 2005 Mar 4;96(4):412-8. Epub 2005 Jan 27. 15677572 Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. 16959974 Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, Goetz R, Mohammadi M, White KE, Econs MJ: A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest. 2007 Sep;117(9):2684-91. 17710231